6625 The epothilone B analogs are non-taxane tubulin stabilizing compounds that are active in taxane-resistant and -sensitive preclinical models. BMS-247550 is a semi-synthetic epothilone B analog that has shown activity in phase I trials against the non-Hodgkin’s lymphomas (NHL). We report a phase II trial of BMS-247550 in relapsed aggressive NHL. Objectives were overall response rate, toxicity, and overall survival. Eligible pts had relapsed aggressive lymphomas, no baseline neuropathy ≥ grade 1, normal organ and bone marrow function, no active CNS disease, HIV negative status, and WHO performance status 0–2. The treatment regimen consisted of BMS-247550 20 mg/m2 given intravenously over 1 hour on Days 1, 8, and 15 of a 28 day cycle on an outpatient basis. Results: To date, 18 pts have been enrolled at 4 institutions. One pt had rapidly progressive disease and died before completing cycle 1. Of 12 pts with a confirmed histologic subtype, 7 had diffuse large B cell lymphoma, 4 had mantle cell lymphoma, 1 pt had follicular grade 3 lymphoma. The median age was 66 years (range, 46–77 years). All pts were heavily pretreated and at least 3 pts had failed a prior autologous stem cell transplant. 15 pts have received a median of 2 cycles (range, 1–4) of BMS-247550. Of 14 evaluable pts, 2 patients have achieved a PR, 6 have stable disease (SD), and 6 pts have progressed. However, of the pts with radiologic SD, at least one pt has become PET negative and has successfully gone on to receive a matched sibling allogeneic transplant. The median time to progression and the progression-free survival are 108 days, and the overall survival is 399 days. 4 pts have died, and 14 pts remain alive. The main toxicities were hematologic (6 pts with grade 3 or 4 neutropenia) and neurologic (5 pts with grade 3 neuropathy), but all toxicity except for a grade 3 unilateral hearing loss resolved to baseline with cessation of drug. 6 pts had either grade 3 (2 pts) or 4 (4 pts) fatigue. In summary, BMS-247550 shows promising activity in a group of heavily pretreated and elderly pts with relapsed aggressive lymphomas, and warrants ongoing study. No significant financial relationships to disclose.